Brummelte S, Mc Glanaghy E, Bonnin A, Oberlander T F
Department of Psychology, Wayne State University, 5057 Woodward Avenue, Detroit, MI 48202, USA.
Department of Pediatrics, University of British Columbia, Vancouver, BC, Canada; Child & Family Research Institute, University of British Columbia, Vancouver, BC, Canada.
Neuroscience. 2017 Feb 7;342:212-231. doi: 10.1016/j.neuroscience.2016.02.037. Epub 2016 Feb 22.
The neurotransmitter serotonin (5-HT) plays a central role in brain development, regulation of mood, stress reactivity and risk of psychiatric disorders, and thus alterations in 5-HT signaling early in life have critical implications for behavior and mental health across the life span. Drawing on preclinical and emerging human evidence this narrative review paper will examine three key aspects when considering the consequences of early life changes in 5-HT: (1) developmental origins of variations of 5-HT signaling; (2) influence of genetic and epigenetic factors; and (3) preclinical and clinical consequences of 5-HT-related changes associated with antidepressant exposure (SSRIs). The developmental consequences of altered prenatal 5-HT signaling varies greatly and outcomes depend on an ongoing interplay between biological (genetic/epigenetic variations) and environmental factors, both pre and postnatally. Emerging evidence suggests that variations in 5-HT signaling may increase sensitivity to risky home environments, but may also amplify a positive response to a nurturing environment. In this sense, factors that change central 5-HT levels may act as 'plasticity' rather than 'risk' factors associated with developmental vulnerability. Understanding the impact of early changes in 5-HT levels offers critical insights that might explain the variations in early typical brain development that underlies behavioral risk.
神经递质5-羟色胺（5-HT）在大脑发育、情绪调节、应激反应性以及精神疾病风险中起着核心作用，因此生命早期5-HT信号的改变对整个生命周期的行为和心理健康具有至关重要的影响。基于临床前和新出现的人体证据，这篇叙述性综述文章将在考虑生命早期5-HT变化的后果时审视三个关键方面：（1）5-HT信号变化的发育起源；（2）遗传和表观遗传因素的影响；以及（3）与抗抑郁药暴露（选择性5-羟色胺再摄取抑制剂）相关的5-HT相关变化的临床前和临床后果。产前5-HT信号改变的发育后果差异很大，其结果取决于出生前后生物学（遗传/表观遗传变异）和环境因素之间持续的相互作用。新出现的证据表明，5-HT信号的变化可能会增加对危险家庭环境的敏感性，但也可能增强对滋养环境的积极反应。从这个意义上说，改变中枢5-HT水平的因素可能作为与发育易损性相关的“可塑性”而非“风险”因素。了解5-HT水平早期变化的影响提供了关键的见解，这可能解释了作为行为风险基础的早期典型大脑发育的差异。
